To Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together

Diabetes Mellitus, Type 2 Clinical Trial

— LEAD-2  

Official title:

Liraglutide Effect and Action in Diabetes (LEAD-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00318461
• Other study ID #: NN2211-1572
• Status: Completed
• Phase: Phase 3
• First received: April 25, 2006
• Last updated: October 14, 2014
• Start date: May 2006
• Est. completion date: November 2008

Study information

• Verified date: October 2014
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesSpain: Spanish Agency of MedicinesCroatia: Ministry of Health and Social CareRussia: Pharmacological Committee, Ministry of HealthDenmark: Danish Medicines AgencyRomania: State Institute for Drug ControlHungary: National Institute of PharmacyBulgaria: Bulgarian Drug AgencySouth Africa: Medicines Control CouncilNetherlands: Dutch Health Care InspectorateArgentina: Administracion Nacional de Medicamentos, Alimentos y TecnologiaItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthIreland: Irish Medicines BoardAustralia: Department of Health and Ageing Therapeutic Goods AdministrationNorway: Norwegian Medicines AgencySweden: Medical Products AgencyIndia: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is designed to show the effect of treatment with liraglutide when adding to existing metformin therapy and to compare it with the effects of metformin monotherapy and combination therapy of metformin and glimepiride. Two trial periods: A 6 month (26 weeks) randomised, double-blinded period followed by an 18 months open-label extension, in total 2 years (104 weeks).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1091
• Est. completion date: November 2008
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects diagnosed with type 2 diabetes and treated with oral anti-diabetic drugs (OADs) for at least 3 months

• HbA1c: 7.0-11.0 % (both incl.) in subjects on OAD monotherapy. 7.0-10.0 % (both incl.) in subjects on OAD combination therapy

• Body Mass Index (BMI) less than or equal 40 kg/m2

Exclusion Criteria:

• Subjects treated with insulin within the last three months

• Subjects with any serious medical condition

• Females of child bearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant or not using adequate contraceptive methods

• Subjects using any drug (except for OADs), which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
0.6 mg for s.c. (under the skin) injection.
• metformin
1.5-2.0 g tablets
• glimepiride
4 mg tablets
• placebo
Glimepiride placebo 1 mg and 2 mg tablets
• placebo
Liraglutide placebo 1-3 mL for s.c. (under the skin) injection
• liraglutide
1.2 mg for s.c. (under the skin) injection
• liraglutide
1.8 mg for s.c. (under the skin) injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Bulgaria,  Croatia,  Denmark,  Germany,  Hungary,  India,  Ireland,  Italy,  Netherlands,  New Zealand,  Norway,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated A1c (HbA1c) at Week 26	Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)	week 0, week 26	No
Primary	Change in Glycosylated A1c (HbA1c) at Week 104	Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)	week 0, week 104	No
Secondary	Change in Body Weight at Week 26	Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)	week 0, week 26	No
Secondary	Change in Body Weight at Week 104	Change in body weight from baseline (week 0) to 104 weeks (end of treatment)	week 0, week 104	No
Secondary	Change in Fasting Plasma Glucose (FPG) at Week 26	Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)	week 0, week 26	No
Secondary	Change in Fasting Plasma Glucose (FPG) at Week 104	Change in Fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of treatment)	week 0, week 104	No
Secondary	Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26	Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.; Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.	week 0, week 26	No
Secondary	Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104	Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of treatment). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.; Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.	week 0, week 104	No
Secondary	Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26	Change in mean post prandial plasma glucose from baseline (Week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.	week 0, week 26	No
Secondary	Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104	Change in mean post prandial plasma glucose from baseline (Week 0) to 104 weeks (end of treatment) The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.	week 0, week 104	No
Secondary	Change in Beta-cell Function at Week 26	Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).; Beta-cell function: HOMA-B (%) = 20·fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).	week 0, week 26	No
Secondary	Change in Beta-cell Function at Week 104	Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).; Beta-cell function: HOMA-B (%) = 20·fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).	week 0, week 104	No
Secondary	Hypoglycaemic Episodes at Week 26	Total number of hypoglycaemic episodes occuring after baseline (week 0) until week 26 (end of randomisation). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.	weeks 0-26	Yes
Secondary	Hypoglycaemic Episodes at Week 104	Total number of hypoglycaemic episodes occuring after baseline (week 0) until 104 weeks (end of treatment). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.	weeks 0-104	Yes

External Links

•   Clinical Trials at Novo Nordisk